5-bromo-1,1,3,3-tetramethyl-2-indanone | 138349-99-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 5-bromo-1,1,3,3-tetramethyl-2-indanone
• 英文别名: 5-bromo-1,1,3,3-tetramethyl-1H-inden-2(3H)-one；5-bromo-1,1,3,3-tetramethylinden-2-one
• CAS: 138349-99-2
• 化学式: C₁₃H₁₅BrO
• 分子量: 267.166
• InChiKey: ZSRPRVAVCOTICX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  5-bromo-1,1,3,3-tetramethyl-2-indanone 在 air 、 magnesium 作用下， 生成 5-hydroxy-1,1,3,3-tetramethyl-2-indanone
  参考文献：
  名称：

  Nitric Oxide Cheletropic Traps (NOCTs) with Improved Thermal Stability and Water Solubility

  摘要：

  The search for nitric oxide cheletropic traps (NOCTs) of the 7,7,8,8-tetraalkyl-o-quinodimethane type which would have properties appropriate for monitoring the formation of nitric oxide in cell cultures and in vivo by magnetic resonance techniques is described. In addition to the necessary condition that a NOCT reacts rapidly with NO to yield a persistent nitroxide radical, two additional properties were sought: (i) thermal stability at the temperature of interest (37 degrees C) and (ii) water solubility. To these ends, a number of 1,1,3,3-tetraalkyl-2-indanones (and a related naphthalene derivative) were synthesized and subjected to UV photolysis in solution, a procedure which generally (though not in all cases) caused the elimination of carbon monoxide and formation of the corresponding o-quinodimethane. The thermal instability of many of these compounds is due to a 1,5-sigmatropic hydrogen atom transfer which, for example, converts 7,7,8,8-tetramethyl-o-quinodimethane (1) to o-isopropyll-alpha-methylstyrene(1P) with a half-life of only ca. 140 s at 37 degrees C. Several o-quinodimethanes were discovered which were, for all practical purposes, completely stable at 37 degrees C. The most suitable lipid-soluble NOCT discovered was 7-(2-indenyl)-7,8,8-trimethyl-o-quinodimethane (5), which is stable and reacts very rapidly with NO to form a persistent nitroxide. Various derivatives of 5 were also examined and found to be equally, or almost equally, effective NOCTs. Water solubility was explored by addition of water-solubilizing groups to the ring of 1. The carboxylic acid group, 13, was found to be particularly suitable, since the carboxylate anion 14 conferred excellent water solubility without,interfering with either the nitric oxide trapping reaction or the necessary photoelimination of carbon monoxide from the starting indanone. Of even greater importance, the carboxylate group had no apparent effect on the rate of the thermal 1,5-sigmatropic rearrangement; i.e., the rates of decay of 14 and 1 were equal within experimental error. It is concluded that NOCTs of the o-quinodimethane class having long lifetimes and a high reactivity toward NO can now be prepared with appropriate lipophilic, hydrophilic, or amphiphilic properties. These NOCTs should prove suitable for exploratory use in biological systems.

  DOI：

  10.1021/ja00086a010
• 作为产物：
  描述：

  1,1,3,4-四甲基-2-茚酮 在 溴 、 铁粉 作用下， 以34%的产率得到5-bromo-1,1,3,3-tetramethyl-2-indanone
  参考文献：
  名称：

  Nitric Oxide Cheletropic Traps (NOCTs) with Improved Thermal Stability and Water Solubility

  摘要：

  The search for nitric oxide cheletropic traps (NOCTs) of the 7,7,8,8-tetraalkyl-o-quinodimethane type which would have properties appropriate for monitoring the formation of nitric oxide in cell cultures and in vivo by magnetic resonance techniques is described. In addition to the necessary condition that a NOCT reacts rapidly with NO to yield a persistent nitroxide radical, two additional properties were sought: (i) thermal stability at the temperature of interest (37 degrees C) and (ii) water solubility. To these ends, a number of 1,1,3,3-tetraalkyl-2-indanones (and a related naphthalene derivative) were synthesized and subjected to UV photolysis in solution, a procedure which generally (though not in all cases) caused the elimination of carbon monoxide and formation of the corresponding o-quinodimethane. The thermal instability of many of these compounds is due to a 1,5-sigmatropic hydrogen atom transfer which, for example, converts 7,7,8,8-tetramethyl-o-quinodimethane (1) to o-isopropyll-alpha-methylstyrene(1P) with a half-life of only ca. 140 s at 37 degrees C. Several o-quinodimethanes were discovered which were, for all practical purposes, completely stable at 37 degrees C. The most suitable lipid-soluble NOCT discovered was 7-(2-indenyl)-7,8,8-trimethyl-o-quinodimethane (5), which is stable and reacts very rapidly with NO to form a persistent nitroxide. Various derivatives of 5 were also examined and found to be equally, or almost equally, effective NOCTs. Water solubility was explored by addition of water-solubilizing groups to the ring of 1. The carboxylic acid group, 13, was found to be particularly suitable, since the carboxylate anion 14 conferred excellent water solubility without,interfering with either the nitric oxide trapping reaction or the necessary photoelimination of carbon monoxide from the starting indanone. Of even greater importance, the carboxylate group had no apparent effect on the rate of the thermal 1,5-sigmatropic rearrangement; i.e., the rates of decay of 14 and 1 were equal within experimental error. It is concluded that NOCTs of the o-quinodimethane class having long lifetimes and a high reactivity toward NO can now be prepared with appropriate lipophilic, hydrophilic, or amphiphilic properties. These NOCTs should prove suitable for exploratory use in biological systems.

  DOI：

  10.1021/ja00086a010

文献信息

• [EN] PHARMACEUTICAL COMPOUNDS AS INHIBITORS OF SPHINGOSINE KINASE<br/>[FR] COMPOSÉS PHARMACEUTIQUES EN TANT QU'INHIBITEURS DE LA SPHINGOSINE KINASE
  申请人：ALMAC DISCOVERY LTD

  公开号：WO2012069852A1

  公开（公告）日：2012-05-31

  The present invention relates to compounds that are useful as inhibitors of the activity of one or more isoforms of sphingosine kinase. Particularly, although not exclusively, the present invention also relates to pharmaceutical compositions comprising these compounds and to the use of these compounds in the treatment and/or prevention of cancers, hyperproliferative, inflammatory, angiogenic, immune and viral infectious diseases.

  本发明涉及一种可用作抑制一种或多种鞘氨醇激酶同工酶活性的化合物。特别是，尽管不仅限于此，本发明还涉及包含这些化合物的药物组合物，以及将这些化合物用于治疗和/或预防癌症、高增殖、炎症、血管生成、免疫和病毒感染性疾病的用途。
• Nitric Oxide Cheletropic Traps (NOCTs) with Improved Thermal Stability and Water Solubility
  作者：H.-G. Korth、R. Sustmann、P. Lommes、T. Paul、A. Ernst、H. de Groot、L. Hughes、K. U. Ingold

  DOI：10.1021/ja00086a010

  日期：1994.4

  The search for nitric oxide cheletropic traps (NOCTs) of the 7,7,8,8-tetraalkyl-o-quinodimethane type which would have properties appropriate for monitoring the formation of nitric oxide in cell cultures and in vivo by magnetic resonance techniques is described. In addition to the necessary condition that a NOCT reacts rapidly with NO to yield a persistent nitroxide radical, two additional properties were sought: (i) thermal stability at the temperature of interest (37 degrees C) and (ii) water solubility. To these ends, a number of 1,1,3,3-tetraalkyl-2-indanones (and a related naphthalene derivative) were synthesized and subjected to UV photolysis in solution, a procedure which generally (though not in all cases) caused the elimination of carbon monoxide and formation of the corresponding o-quinodimethane. The thermal instability of many of these compounds is due to a 1,5-sigmatropic hydrogen atom transfer which, for example, converts 7,7,8,8-tetramethyl-o-quinodimethane (1) to o-isopropyll-alpha-methylstyrene(1P) with a half-life of only ca. 140 s at 37 degrees C. Several o-quinodimethanes were discovered which were, for all practical purposes, completely stable at 37 degrees C. The most suitable lipid-soluble NOCT discovered was 7-(2-indenyl)-7,8,8-trimethyl-o-quinodimethane (5), which is stable and reacts very rapidly with NO to form a persistent nitroxide. Various derivatives of 5 were also examined and found to be equally, or almost equally, effective NOCTs. Water solubility was explored by addition of water-solubilizing groups to the ring of 1. The carboxylic acid group, 13, was found to be particularly suitable, since the carboxylate anion 14 conferred excellent water solubility without,interfering with either the nitric oxide trapping reaction or the necessary photoelimination of carbon monoxide from the starting indanone. Of even greater importance, the carboxylate group had no apparent effect on the rate of the thermal 1,5-sigmatropic rearrangement; i.e., the rates of decay of 14 and 1 were equal within experimental error. It is concluded that NOCTs of the o-quinodimethane class having long lifetimes and a high reactivity toward NO can now be prepared with appropriate lipophilic, hydrophilic, or amphiphilic properties. These NOCTs should prove suitable for exploratory use in biological systems.